The primary objectives of the proposed studies are to elucidate the metabolic pathways involved in the conversion of cholesterol to bile acids in man. It is planned to integrate these findings into our recently defined multicompartmental cholesterol system with particular emphasis on the hepatic regulation of cholesterol metabolism. The initial experiments will be a continuation of the present studies being carried out in patients with biliary diversion. Specifically, various labeled bile acid (a potential) intermediates will be administered i.v. and their rapidity and efficiency of conversion to cholic and chenodeoxycholic acid determined. When sufficient information has been an intact enterohepatic circuit; these patients will receive labeled intermediates plus 14C-cholic and 14C-chenodeoxycholic acid. Fractional conversion of the labeled intermediates will be estimated from areas under the specific activity curves as well as from 14C-kinetic and bile acid pool data. This will then be compared to the ratio of cholic to chenodeoxycholic acid synthesis. It is also planned to carry out precursor-product studies in patients with T-tubes; bile acid intermediates will be isolated and characterized from human hepatic bile and their labeled patterns determined. These studies may provide important information on bile acid pathways and have important implications for cholesterol regulation in man.